第三阶段NEPTUNE研究（NCT02542293）评估了一线用durvalumab加tremelimumab（DT）与化疗治疗转移性非小细胞肺癌的疗效。事先规定探索性分析在中国扩大群体中进行。病人按PD-L1肿瘤细胞（TC）表达（≥25％与<25％）、组织学及吸烟史分层，随机（1：1）接受DT或标准化疗。此群体的主要分析是PD-L1 TC <1％的患者的总体生存期（OS）。次要分析包括ITT人群和PD-L1亚组的OS、无进展生存期（PFS）以及安全性。这些群体分析没有分配α值（数据截止日期为2020年9月21日）。78名和82名患者分别接受DT和化疗随机分组，其中26名和29名PD-L1 TC <1％（中位随访时间为31.2和29.7个月[被审查病人]）。在PD-L1 TC <1％的患者中，DT的OS优于化疗（HR 0.60；95％CI，0.32-1.11），分别为15.0个月（95％CI，10.5-27.4）和11.7个月（95％CI，8.6-20.5）；24个月的比率分别为36.0％（95％CI，18.2-54.2）和17.9％（95％CI，6.5-33.7）。在ITT人群中，DT的OS比化疗延长（HR 0.70；95％CI，0.48-1.02），中位生存期分别为20.0和14.1个月，24个月的生存率分别为44.2％和30.4％。 在PD-L1 TC <1％（HR 1.13；95％CI，0.59-2.14）和ITT（HR 0.95；95％CI，0.66-1.36）人群中，PFS相似；12个月的比率分别为15.6％和11.3％以及23.9％和16.6％。DT组的三四级治疗相关不良事件(TRAEs)发生率为31.2％，化疗组为52.6％，而因TRAEs停药的比例分别为3.9％和10.3％。探索性分析显示，首线DT在中国PD-L1 TC <1％人群和ITT人群中，相较于化疗，OS有改善的趋势，24个月OS和12个月PFS的比率表明生存曲线尾部受益。DT耐受性良好，没有新的安全信号。 版权所有©2023 The Authors。发表于Elsevier B.V.。保留所有权利。

The phase 3 NEPTUNE study (NCT02542293) evaluated first-line durvalumab plus tremelimumab (DT) versus chemotherapy for metastatic NSCLC. Prespecified exploratory analyses were conducted in an extended cohort enrolled in China.Patients were randomized (1:1) to DT or standard chemotherapy, stratified by PD-L1 tumor cell (TC) expression (≥25 % vs < 25 %), histology, and smoking history. The primary analysis for this cohort was overall survival (OS) in patients with PD-L1 TC < 1 %. Secondary analyses included OS and progression-free survival (PFS) in the ITT population and PD-L1 subgroups, and safety. No alpha was allocated to these cohort analyses (data cut-off, 21-September-2020).78 and 82 patients were randomized to DT and chemotherapy, respectively; 26 and 29 had PD-L1 TC < 1 % (median follow-up, 31.2 and 29.7 months [censored patients]). Among patients with PD-L1 TC < 1 %, OS favored DT versus chemotherapy (HR 0.60; 95 % CI, 0.32-1.11), with medians of 15.0 months (95 % CI, 10.5-27.4) and 11.7 months (95 % CI, 8.6-20.5), respectively; 24-month rates were 36.0 % (95 % CI, 18.2-54.2) and 17.9 % (95 % CI, 6.5-33.7). In the ITT population, OS was prolonged with DT versus chemotherapy (HR 0.70; 95 % CI, 0.48-1.02); medians were 20.0 and 14.1 months and 24-month rates were 44.2 % and 30.4 %. PFS was similar in the PD-L1 TC < 1 % (HR 1.13; 95 % CI, 0.59-2.14) and ITT (HR 0.95; 95 % CI, 0.66-1.36) populations; 12-month rates were 15.6 % versus 11.3 % and 23.9 % versus 16.6 %. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 31.2 % with DT and 52.6 % with chemotherapy; 3.9 % versus 10.3 % discontinued due to TRAEs.In exploratory analyses, first-line DT showed a trend towards improved OS versus chemotherapy among Chinese patients in the PD-L1 TC < 1 % population and ITT population, with 24-month OS and 12-month PFS rates indicating benefit in survival curve tails. DT was well tolerated with no new safety signals.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.